A Study to Evaluate the Safety, Efficacy, Tolerability and Pharmacokinetics of Escalating Doses of Glofitamab (RO7082859) as a Single Agent and in Combination with Obinutuzumab, Administered After a Fixed, Single Dose Pre-treatment of Obinutuzumab (Gazyva®/Gazyvaro™) in Patients with Relapsed/Refractory B-Cell Non-Hodgkin’s Lymphoma

Overview

Sponsor-declared trial summary

Key facts

Sponsor

F. Hoffmann-La Roche AG

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Psychiatry and Psychology [F] - Behavioral Disciplines and Activities [F04]

Trial duration

31 Jan 2017 → ongoing

Decision date (initial)

2024-08-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

F. Hoffmann-La Roche AG

External identifiers

EU CT number

2023-505625-14-00

EudraCT number

2016-001185-28

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacodynamic, Pharmacokinetic, Efficacy

To determine:
 the maximal tolerated dose or optimal biologic dose and dose-limiting toxicity of glofitamab as single agent and in combination with obinutuzumab following Gpt in patients with r/r NHL
 a recommended dose and schedule of glofitamab as single agent and in combination with obinutuzumab following Gpt
To evaluate:
 The safety, tolerability, and pharmacokinetic (PK) of glofitamab as single agent and in combination with obinutuzumab following obinutuzumab pretreatment (Gpt) in patients with r/r (CD)20 + B-cell NHL
 The efficacy of glofitamab as single agent following Gpt in patients in patients with Diffuse large B-cell lymphoma, and in patients with r/r Follicular lymphoma (FL) measured by Independent Review Committee (IRC)-assessed complete response rate (CRR) according to Lugano 2014 Classification
 To evaluate the efficacy of glofitamab as single agent following Gpt and/or dGpt in R/R MCL patients by IRC-assessed CRR according to Lugano Classification

Secondary objectives 5

1. To establish the safety, tolerability, PK of Gpt
2. To make a preliminary assessment of the anti-tumor activity of glofitamab as single agent and in combination with obinutuzumab following Gpt in patients with r/r NHL
3. To assess the incidence of anti-drug antibodies (ADA) to glofitamab
4. To assess pharmacodynamic biomarkers, including but not limited to tumor tissue B-and T-cell content and T-cell activation status in a subset of patients
5. In Part III of the study, to assess disease-related symptoms, function, and health-related quality of life according to the European organization for research and treatment of cancer quality of Life questionnaire core 30; and functional assessment of cancer therapy-lymphoma scale

Conditions and MedDRA coding

Relapsed/refractory B-cell non-Hodgkin’s lymphoma (r/r NHL)

Study design 3 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Patient willing and able to comply with protocol-mandated hospitalizations upon administration of glofitamab and also all study-related procedures, in Part III, this includes completion of Patient-reported outcome
2. For Parts I and II:Grades 1-3b FL; Marginal zone lymphoma; Mantle cell lymphoma; DLBCL; Primary mediastinal B-cell lymphoma; Richter’s transformation; and transformed FL (trFL) For Part III expansion cohorts: DLBCL cohort (r/r DLBCL, not otherwise specified [NOS]/high-grade B-cell lymphoma [HGBCL],PMBCL and trFL). Patients must have relapsed after or failed to respond to at least two prior systemic treatment regimens (including at least one prior regimen containing anthracycline, and at least one containing an anti CD20-directed therapy). cohort: R/R FL cohort: Grades 1-3a FL patients must have relapsed after or failed to respond to at least two prior lines of systemic therapy and must have received prior treatment with rituximab and alkylating agents
3. For Part III expansion cohorts: Life expectancy (in the opinion of the Investigator) of >= 12 weeks
4. Measurable disease, defined as at least one bi-dimensionally measurable nodal lesion, defined as >1.5 cm in its longest dimension, or at least one bi-dimensionally measurable extranodal lesion, defined as >1.0 cm in its longest dimension
5. Eastern Cooperative Oncology Group performance status of 0 or 1
6. Adequate liver, hematological, and renal function

Exclusion criteria 6

1. Inability to comply with protocol mandated hospitalization and restrictions
2. Patients with chronic lymphocytic leukemia (CLL), Burkitt lymphoma and lymphoplasmacytic lymphoma
3. Patients with a known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
4. Patients with acute bacterial, viral, or fungal infection at baseline, confirmed by a positive blood culture within 72 hours prior to Gpt infusion or by clinical judgment in the absence of a positive blood culture
5. Patients with known active infection, or reactivation of a latent infection, whether bacterial, viral, fungal, mycobacterial, or other pathogens or any major episode of infection requiring hospitalization or treatment with IV antibiotics within 4 weeks of dosing
6. Pregnant, breast-feeding or intending to become pregnant during the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 13

1. 1. Incidence of dose-limiting toxicity (DLTs)
2. 2. The primary safety endpoints will be incidence of all adverse events, changes in vital signs, clinical laboratory values, electrocardiograms and incidence of DLTs
3. 3. Incidence, nature, and severity of all adverse events
4. 4. Incidence of cytokine-release related events (cytokine-release syndrome [CRS] and infusion-related reactions [IRRs]) according to the grading criteria in Lee (2014)
5. 5. Changes in clinical laboratory values: hematology and biochemistry test results
6. 6. Changes in vital signs, including systolic and diastolic blood pressure, respiratory rate, pulse rate, and body temperature
7. 7. Incidence of ECG abnormality
8. 8. Total exposure (area under the concentration-time curve [AUC]) of glofitamab
9. 9. Maximum serum concentration (Cmax) of glofitamab
10. 10. Minimum serum concentration (Cmin) of glofitamab
11. 11. Clearance (CL) of glofitamab
12. 12. Volume of distribution (Vz) of glofitamab
13. 13. Independent Review Committee (IRC)-assessed CR rate using Lugano criteria

Secondary endpoints 14

1. 1. Investigator (INV)-assessed CR rate (Lugano classification)
2. 2. IRC-assessed overall response rate (ORR) (Lugano classification)
3. 3. INV-assessed ORR (Lugano classification)
4. 4. IRC - and INV-assessed duration of complete response (Lugano Classification)
5. 5. IRC- and INV-assessed duration of response (Lugano classification)
6. 6. IRC-assessed progression-free survival (PFS) and INV-assessed PFS (Lugano classification)
7. 7. IRC-assessed time to first complete response (TFCR) (Lugano classification)
8. 8. INV-assessed TFCR (Lugano classification)
9. 9. IRC-assessed time to first overall response (TFOR) (Lugano classification)
10. 10. INV-assessed TFOR (Lugano classification)
11. 11. Overall survival
12. 12. Change from baseline in physical function, role function, and health-related quality of life European organization for research and treatment of cancer quality of Life questionnaire core 30 based on European organization for research and treatment of cancer quality of Life questionnaire core 30
13. 13. Change from baseline in disease-related symptoms based on the functional assessment of cancer therapy-lymphoma scale
14. 14. Incidence of ADA formation and events related to immune complex deposition and activation

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Auxiliary 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

F. Hoffmann-La Roche AG

Sponsor organisation

F. Hoffmann-La Roche AG

Address

Grenzacherstrasse 124

City

Basel

Postcode

4058

Country

Switzerland

Scientific contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Public contact point

Organisation

F. Hoffmann-La Roche AG

Contact name

Trial Information System - TISL

Third parties 15

Locations

8 EU/EEA countries · 22 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 73 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications